key: cord-0740969-2viueaag
authors: Ota, K.; Yanagihara, K.; Murakami, S.; Mukae, H.; Kohno, S.
title: Measurement of multiple SARS-CoV-2 antibody titer after vaccination represents individual vaccine response and contributes to individually appropriate vaccination schedules
date: 2021-05-23
journal: nan
DOI: 10.1101/2021.05.21.21257575
sha: 8658ada7b8f82be4dd2911e07b7fe15cad43636e
doc_id: 740969
cord_uid: 2viueaag

mRNA vaccine (BNT162b2) induces antibodies against Spike protein produced by host cell. However, multiple antibody responses before and after vaccination have not been clarified. To clarify multiple antibody responses after mRNA vaccination in a variation of individuals including prior infection of COVID-19. This is a prospective, observational study, started from March 15th, 2021. IgG and IgM against Receptor Binding Domain (RBD), and IgG against Nucleocapsid protein (N) were measured by chemiluminescence immunoassay (Alinity, Abbott) in the following schedules; before vaccination, and 7, 14, 28 days, 12, 24, 36, 48 weeks after 1st vaccination. A total of 136 vaccinees (including 23 of those with prior infection) were enrolled in this analysis. Single-dose vaccination in participants with prior infection yielded higher IgG (RBD) response than two-dose vaccination in participants without prior infection (mean {+/-} standard deviation, 31,523 {+/-} 14,332 arbitrary units [AU] per mL vs. 22,461 {+/-} 15,661 AU/mL, P = 0.01). IgM (RBD) response was observed in participants without prior infection at 14 days after the first vaccination, achieving a comparable antibody titer compared with those with prior infection (1.41 {+/-} 1.93 chemiluminescence of Sample / Calibrator [S/C] vs. 1.96 {+/-} 2.49 S/C, P = 0.24). IgG (N) showed its specificity and usefulness to differentiate those with and without prior infection, regardless of vaccination. We investigated the participants without prior infection to analyze antibody response according to backgrounds. IgG (RBD) response was significantly lower in those [greater double equals] 40 years old than those < 40 years old (19,087 {+/-} 14,630 AU/mL vs. 25,334 {+/-} 15,849 AU/mL, P = 0.04) at 28 days after 1st vaccination. Low antibody responses were observed in vaccinees with underlying disease or immunosuppressive therapy. Multiple antibody dynamics of vaccinees were clarified in this study. Monitoring each person's antibody titer is warranted in public with expected low and high responders. However, we have yet to observe antibody duration of vaccinees. Therefore, effectiveness of single dose vaccination against those with prior infection is not assessed. Antibody titer follow-up study is in progress.

the establishment of personally customized schedules, including antibody follow-up, and will balance both faster delivery of vaccines and confirmation of effective vaccination.

We have been conducting a prospective study to evaluate antibody response after vaccination in healthcare workers with (n=23) and without (n=113) prior COVID-19 infection Baseline antibody profiles of the participants with prior infection indicated that IgG (RBD) peaked after 12-24 weeks of natural infection, IgM (RBD) showed a consistent decrease, and IgG (N) significantly decreased at more than 24 weeks of past infection (figure A). As concordant with previous reports 2-5 , single-dose vaccination in participants with prior infection yielded comparable or higher IgG (RBD) response to two-dose vaccination in . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) mofetil. The latter did not achieved immunization even at 7 days after 2 nd vaccination. From the viewpoint of the relationship between age and antibody response, age was inversely correlated with IgG (RBD) antibody response. We divided participants without prior infection into two groups (≥40 years and <40 years) to assess the differences in antibody response according to age (figure E). IgG (RBD) response was significantly lower in those >40 years old (19,087 ± 14,630 AU/mL vs. 25,334 ± 15,849 AU/mL, P = 0·04).

. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 23, 2021. ; https://doi.org/10.1101/2021.05.21.21257575 doi: medRxiv preprint According to our results, personal customized vaccination schedules together with appropriate follow-up may be proposed as follows.

Single-dose vaccination may be warranted for those with prior COVID-19 infection if an adequate antibody titer is confirmed. For persons with underlying diseases (e.g., rheumatoid disease, collagen diseases, or hemodialysis), follow-up by antibody measurement may be considered. Age in the forties can be considered a predictive factor for lower antibody response.

In addition, this observational study suggests that when evaluating antibody responses induced by vaccines, measuring IgG (RBD) is more useful than other antibodies, since IgG (RBD) showed evident response.

The compatibility of both speedy vaccine delivery and effective vaccination schedules is our top concern in conquering COVID-19. We must pay close attention to adapting evidence to clinical practice, since it may unexpectedly lead to worse outcomes of ineffective vaccination. Therefore, our argument is that monitoring each person's antibody titer is warranted in public with expected low and high responders. Further continuous observation (up to 48 weeks) is in progress to confirm the duration of the antibody response obtained by vaccination.

Declaration of interests: MS is an employee of Abbott Japan LLC. YK received research . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. A part of this study was funded by Abbott Japan LLC.

. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. We applied a t-test to assess the differences between groups. (E) IgG (RBD) in individuals without prior COVID-19 infections are shown. They were divided into two groups (≥40 years old and <40 years old, n=47 and 63, respectively, one low responder was excluded from <40 years old group) according to the age at vaccination. We applied . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 23, 2021. ; 9 a t-test to assess the differences between groups.

. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 23, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 23, 2021. 

COVID-19) vaccinations

Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2